The long-term objectives of this project are to identify the mechanisms responsible for hemodynamic changes that occur during digestion, and to determine the relationship between intestinal blood blow and its functions. Since we eat at regular intervals and digestion lasts for 3-4 hours, the body is continuously subjected to the influence of digestion throughout a large part of the day. Furthermore, since a few pathological states, e.g., angina pectoris and intestinal angina, frequently occur after a meal, digestion may be a precipitating cause of their onsets. The specific aims of the present proposal are to determine the roles of prostaglandins, adenosine, and capillary transport in regulation of intestinal blood flow, oxygenation, and absorption during digestion. The effects of luminal placement or instillation of various nutrient solutions on the following variables will be determined: jejunal blood flow, arteriovenous oxygen content difference, oxygen consumption, net transmucosal fluid transport, lumen pressure, glucose and oleic acid absorptions, capillary pressure, capillar filtration coefficient, permeability-surface area product for rubidium, venous blood concentrations of adenosine, PGI2, thromboxane A2, PGF2Alpha, and PGE2 (the rates of their releases will be calculated). In addition, blood flows of the jejunal mucosa and muscularis will be measured by the microsphere method. The above variables will be measured before and after administration of aminophylline, an adenosine receptor antagonist, 1, 3-diethyl-8-phenylxanthine, a more specific adenosine antagonist, dipyridamole, an inhibitor of adenosine degradation, mefenamic acid, a prostaglandin synthesis inhibitor, imidazole, a throboxane synthetase inhibitor, or 15-hydroperoxyarachidonic acid, a prostacyclin synthetase inhibitor. The relation between changes in the above variables, for example, changes in blood flow vs adenosine release will be determined. The effects of various nutrients on syntheses of the above prostaglandins in the jejunal micosal and muscle tissues will be also determined in vitro. The nutrients to be studied are: a diet containing equal parts by weight of fat, protein, carbohydrate, solutions of glucose, oleic acid, and amino acids, and high-fat, high-protein and high-carbohydrate diets.